240 - Efficacy and Safety of All-Site Radiation Therapy and Standard of Care Therapy with or without Docetaxel for Hormone-Sensitive High Gleason Score Prostate Cancer: 6-Year Results from a Long-Term Study

Purpose/Objective(s):

Androgen deprivation therapy (ADT), novel hormonal therapy (NHT), and prostate radiation therapy (RT), have become the standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, for high Gleason score prostate cancer, more intensified systemic and local treatment strategies may be required. The objective of this study is to evaluate the efficacy and safety of combining all-site radiation therapy, with or without docetaxel (Doc) chemotherapy, in conjunction with standard of care therapy (SOC) for high Gleason score mHSPC.

Materials/Methods:

This study consecutively enrolled patients from 2018 to 2024 diagnosed with prostate adenocarcinoma (grade group 5 or including a 5-score component). All participants had confirmed distant metastases via imaging and were in the HSPC stage before radiation therapy. Patients were assigned to either a SOC (ADT + NHT) + all-site RT group, or a SOC + all-site RT + Doc group. The radiation therapy protocol included all-site radiation or targeting all residual sites following systemic therapy. The primary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS). Secondary endpoints included disease-specific survival, PSA progression-free survival, castration-resistant prostate cancer (CRPC)-free survival, time to new anti-cancer treatment, skeletal event-free survival, and urinary symptom deterioration-free survival. Statistical analyses were performed using the Kaplan-Meier method, log-rank test, and Cox regression analysis.

Results:

166 patients were included, 39 in the SOC + all-site RT + Doc group and 127 in the SOC + all-site RT group. The median age was 67 (46-89) years, and the median follow-up time was 18.2 (0.8-76.8) months, including 72 (43.4%) with high tumor burden. The 6-year rPFS was significantly better with Doc (70.6% vs. 54.0%, p=0.039). 78 patients were obtained using 1:1 propensity matching based on 10 baselines, including metastasis type, tumor burden, and others. In the matched population, the SOC + all-site RT + Doc group had significantly better 6-year rPFS (p=0.0092) and CRPC-free survival (p=0.027). Subgroup analyses suggested a significant benefit in 6-year rPFS (p<0.05) and CRPC-free survival (p<0.05) for patients with high tumor burden, synchronous metastasis, and those with an untreated primary site. The skeletal event-free survival (p = 0.95) and urinary symptom deterioration-free survival (p = 0.4) did not differ significantly between the two groups.

Conclusion:

Long-term survival results suggest that intensive docetaxel treatment with all-site radiation therapy, combined with SOC, provides significant rPFS and CRPC-free survival benefits in patients with high Gleason score mHSPC. This effect is more pronounced in subgroups such as those with high tumor burden, synchronous metastasis, and untreated primary sites, with tolerable adverse effects. Further, follow-up is needed to assess PCSS and OS outcomes.